ABSTRACT: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complex disease with progressive right ventricular (RV) failure and pulmonary endarterectomy (PEA) is an established treatment for these patients. To elucidate the molecular changes underlying RV remodeling in patients with CTEPH and the effect of PEA, RNA-sequencing (RNA-seq) was performed on the RV free wall of patients with CTEPH prior to PEA in both exploratory (A-prePEA_RV, n=14) and confirmatory cohorts (B-prePEA_RV, n=71). The gene expression profile of RV free wall in patients with CTEPH in the confirmatory cohort (B-prePEA_RV) was compared with control RV samples (Control_RV, n=10). To determine the effect of PEA on the gene expression profile of the septum, septal biopsies were taken from three pre-PEA patients (B-prePEA_septum, n=3). RNA-seq was performed on these biopsies (B-prePEA_septum, n=3) and they were compared with septal biopsies after PEA (B-postPEA_septum, n=3) and the control septum (Control_septum, n=10). Additionally, tissue biopsies originating from the same patients were analyzed to determine how PEA altered them. This was done by comparing the RNA-seq data of B-prePEA_septum (n=3) with B-prePEA_RV (n=3), and B-prePEA_RV (n=3) with B-postPEA_septum(n=3). Due to clinical restrictions, a direct comparison between prePEA and postPEA septal biopsies was only possible in three CTEPH patients. To extend this study, in a subgroup of 24 patients, the septum biopsies were obtained 12 months postPEA (B-postPEA_septum, n=24). A pairwise comparison was performed between B-postPEA_septum (n=21) and their corresponding RV biopsies (B-prePEA_RV, n=21). Our study identified a profile of gene expression changes and myocardial as well as extracellular matrix remodeling events, underlying the maladaptive RV response to increased afterload and its reversibility upon unloading, offering novel targets for therapeutic intervention.
This repository contains scripts used to analyze data sets described in this study. We applied a range of existing tools for calculations and visualizations. The repository is divided into separate folders containing miscellaneous scripts (misc) and code specific to data types (RNA-Seq).